Propargyl Amides as Irreversible Inhibitors of Cysteine Proteases-A Lesson on the Biological Reactivity of Alkynes

被引：21

作者：

Arkona, Christoph ^{[1
]}

Rademann, Joerg ^{[1
]}

机构：

[1] Free Univ Berlin, Inst Pharm, D-14195 Berlin, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2013年 / 52卷 / 32期

关键词：

bioorthogonality; irreversible inhibitors; proteases; protein-templated reactions; ubiquitin;

D O I：

10.1002/anie.201303544

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Are aliphatic alkynes truly bioorthogonal? In an attempt to prepare clickable ubiquitin derivatives bearing a C-terminal propargyl amide, two groups have now independently discovered propargylamides to be irreversible inhibitors of cysteine proteases. The unexpected findings demonstrate the unexpected reactivity of alkynes in protein-templated reactions and introduce a novel class of activity-based protein probes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：8210 / 8212

页数：3

共 16 条

[1]

[Anonymous], 2009, ANGEW CHEM INT ED, V48, P6974

[2]

[Anonymous], 2010, ANGEW CHEM INT ED, V49, P10149

[3]

[Anonymous], 2009, ANGEW CHEM INT ED, V48, P6346

[4]

Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme [J].

Borodovsky, A ;

Ovaa, H ;

Kolli, N ;

Gan-Erdene, T ;

Wilkinson, KD ;

Ploegh, HL ;

Kessler, BM .

CHEMISTRY & BIOLOGY, 2002, 9 (10) :1149-1159

[5]

Regulation of cellular responses by deubiquitinating enzymes: an update [J].

Burrows, James F. ;

Johnston, James A. .

FRONTIERS IN BIOSCIENCE-LANDMARK, 2012, 17 :1184-1200

[6]

Eger S, 2012, METHODS MOL BIOL, V832, P589, DOI 10.1007/978-1-61779-474-2_41

[7]

On Terminal Alkynes That Can React with Active-Site Cysteine Nucleophiles in Proteases [J].

Ekkebus, Reggy ;

van Kasteren, Sander I. ;

Kulathu, Yogesh ;

Scholten, Arjen ;

Berlin, Ilana ;

Geurink, Paul P. ;

de Jong, Annemieke ;

Goerdayal, Soenita ;

Neefjes, Jacques ;

Heck, Albert J. R. ;

Komander, David ;

Ovaa, Huib .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (08) :2867-2870

[8]

El Oualid F., 2010, Angewandte Chemie, V122, P10347, DOI DOI 10.1002/ANGE.201005995

[9]

Inhibition of human caspases by peptide-based and macromolecular inhibitors [J].

Garcia-Calvo, M ;

Peterson, EP ;

Leiting, B ;

Ruel, R ;

Nicholson, DW ;

Thornberry, NA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (49) :32608-32613

[10]

Emerging roles of desumoylating enzymes [J].

Kim, Jung Hwa ;

Baek, Sung Hee .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (03) :155-162

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